Behavioral effects of 5-methoxy-N,N-dimethyltryptamine and dose-dependent antagonism by BC-105.

The discriminative effects of 5-methoxy-N,N-dimethyltryptamine (5-OMeDMT) were studied in rats trained to discriminate 1.5 mg/kg or 3.0 mg/kg 5-OMeDMT from saline. A series of antagonist and generalization tests revealed that (1) antagonism of the 5-OMeDMT stimulus response by the presumed serotonin antagonist BC-105 depended on the dose of 5-OMeDMT, (2) the 5-OMeDMT stimulus generalized to LSD, and (3) like 5-OMeDMT, antagonism of the LSD generalization response by BC-105 depended on the dose of LSD. In a second study, with rats responding under a variable-interval (VI) 15-s schedule of reinforcement, doses of 1.0-3.0 mg/kg 5-OMeDMT significantly decreased response rate. Furthermore, the decrease in responding produced by the administration of 1.5 mg/kg (but not by 3.0 mg/kg) 5-OMeDMT was blocked by BC-105. This dose-dependent antagonism was of particular interest since the 1.5 mg/kg and 3.0 mg/kg dose of 5-O-MeDMT had essentially the same effect on responding when given alone. The results of both studies emphasize the importance of 5-OMeDMT dose in antagonism experiments.